Maternal smoking and oral clefts: the role of detoxification pathway genes.
ABSTRACT There is evidence for an effect of cigarette smoking on risk of oral clefts. There are also hypothetical pathways for a biologic effect involving toxic chemicals in cigarette smoke.
We performed a combined case-control and family-triad study of babies born with oral clefts in Norway in the period 1996 to 2001, with 88% participation among cases (n = 573) and 76% participation among controls (n = 763). Mothers completed a questionnaire 4 months after birth of the baby. DNA was collected from parents and children, and assayed for genes related to detoxification of compounds of cigarette smoke (NAT1, NAT2, CYP1A1, GSTP1, GSTT1, and GSTM1).
For isolated cleft lip (with or without cleft palate) there was a dose-response effect of smoking in the first trimester. The odds ratio rose from 1.6 (95% confidence interval = 1.0-2.5) for passive smoking to 1.9 (0.9-4.0) for mothers who smoked more than 10 cigarettes per day. There was little evidence of an association with cleft palate. Genetic analyses used both case-control and family-triad data. In case-triads we found an association between a NAT2 haplotype and isolated cleft lip (relative risk of 1.6 with 1 copy of the allele and 2.5 with 2 copies), but with little evidence of interaction with smoking. Other genes did not show associations, and previously described interactions with smoking were not confirmed.
First-trimester smoking was clearly associated with risk of cleft lip. This effect was not modified by variants of genes related to detoxification of compounds of cigarette smoke.
SourceAvailable from: Mona Hassan Ahmed Hassan[Show abstract] [Hide abstract]
ABSTRACT: Studies have found a consistent positive association between maternal smoking and non-syndromic orofacial clefts (NSOFC). However, no comprehensive assessment of the association between NSOFC and passive smoking has been undertaken. This systematic review and meta-analysis explores the relationship between maternal passive smoking and NSOFC, and compares the associations between passive and active smoking. Search strategy, inclusion / exclusion criteria, and data extraction from studies reporting maternal passive smoking and NSOFC was implemented without language restrictions. Risks of bias in the identified studies were assessed and this information was used in sensitivity analyses to explain heterogeneity. Meta-analysis and meta-regression of the extracted data were performed. Egger's test was used to test for small study effects. Fourteen eligible articles were identified. Maternal passive smoking exposure was associated with a twofold increase in risk of NSOFC (odds ratio: 2.11, 95% confidence interval: 1.54-2.89); this was apparent for both cleft lip with and without palate (OR: 2.05, 95% CI: 1.27-3.3) and cleft palate (OR: 2.11, 95% CI: 1.23-3.62). There was substantial heterogeneity between studies. In the studies that provided data enabling crude and adjusted odd ratios to be compared, adjustment for potential confounders attenuated the magnitude of association to about a 1.5-fold increase in risk. Overall, maternal passive smoking exposure results in a 1.5 fold increase in risk of NSOFC, similar to the magnitude of risk reported for active smoking, but there is marked heterogeneity between studies. This heterogeneity is not explained by differences in the distribution of cleft types, adjustment for covariates, broad geographic region, or study bias/quality. This thorough meta-analysis provides further evidence to minimize exposure to environmental tobacco smoke in policy making fora and in health promotion initiatives.PLoS ONE 03/2015; 10(3):e0116963, 21 pages. DOI:10.1371/journal.pone.0116963 · 3.53 Impact Factor
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ABSTRACT: The increasing use of tobacco among youths warrants the need for dental health professionals to effectively provide tobacco cessation counselling (TCC) in the office and community settings. However, there have been concerns among the dental professionals regarding TCC in dental settings.
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ABSTRACT: Background Exposure of pregnant mice to corticosteroids can produce oral clefts in offspring. While data in humans are more mixed, recent reports have suggested that dermatologic steroids are associated with oral clefts. Methods We investigated maternal first-trimester exposure to corticosteroids (focusing on dermatologic uses) and oral clefts in offspring using two population-based studies. The Norway Cleft Study (1996-2001) is a national case-control study including 377 infants with cleft lip +/- palate (CLP), 196 infants with cleft palate only (CPO) and 763 controls. The Norwegian Mother and Child Cohort Study (MoBa, 1998-2008), is a national birth cohort including 123 infants with CLP, 61 infants with CPO and 551 controls. Results In the case-control study, there was the suggestion of an association of dermatological corticosteroids with both CLP (adjusted OR (aOR) = 2.3, 95% confidence interval = 0.71, 7.7) and CPO (aOR = 3.4, 0.87-13). There was no evidence of this association in the cohort data (OR for CLP = 1.2; 0.50, 2.8), OR for CPO = 1.0, 0.30-3.4), although exposure to dermatological steroids was less specifically ascertained. There were no associations with other types of corticosteroids. Conclusion Our data add to the suggestive but inconsistent findings for this association.Annals of Epidemiology 09/2014; 24(9). DOI:10.1016/j.annepidem.2014.06.005 · 2.15 Impact Factor